Characterization of a rat hypoxia-ischemia model where duration of hypoxia is determined by seizure activity

Perinatal and early childhood asphyxia is common, debilitating and has few efficacious treatments. A hypoxia ischemia (HI) rat model that involves a unilateral ligation of the common carotid artery followed by a 60 min period of 8% oxygen hypoxia is often used to test proposed treatments. However, this HI protocol produces inconsistent infarction volumes due to the variability of individual rats to compensate for the ligated artery and hypoxia. Therefore, this HI model is problematic for experiments that prevent measurement of infarction volume, such as those that require analysis of homogenised brain tissue. We therefore aimed to find a simple and non-invasive predictor of infarction volume. Observations made prior, during and following HI in p26 rats showed that weight change 24 h following surgery was a strong predictor of infarction volume. The occurrence of a tonic clonic seizure during hypoxia was highly correlated with success of inducing an infarction, and for this reason we assessed whether ceasing the hypoxia for each rat following a tonic clonic seizure would produce a more consistent infarction volume. Using this procedure, infarction volumes measured at 3 and 15 days after surgery were significantly less variable, resulting in considerable improvements in statistical power compared with the original model.